The goal of this application is to develop the biomedical research skills-of the candidate, Dr. Jingly Weier, who holds a Ph.D. in chemical engineering. The laboratory portion of the training experience will focus on the human placenta; studies to correlate placental karyotype/genotype with the phenotype of the component cells are proposed. The candidate will also acquire formal academic training in cytogenetics. Currently, Dr. Weier is working in the Division of Reproductive Genetics at the University of California San Francisco (UCSF). To become an independent investigator she needs additional research experience in the biomedical sciences and training in cytogenetics. Toward this end she has enlisted the guidance of two mentors who are senior members of the UCSF faculty. Dr. Susan Fisher is an expert in placental cell biology and Dr. Roger Pedersen is an authority on the molecular genetics of early development. The environment at UCSF is highly conducive to completing the objectives of this application. Necessary elements include the high caliber of ongoing research in reproductive biology and core facilities for genetic analyses. The requisite teaching programs are also in place. As to specifics, the candidate will enroll in a two-year cytogenetics training program and take the Medical Genetics Board Certification exam. At the same time she will conduct research that addresses important unanswered questions about the rate and consequences of karyotypic/genetic abnormalities in cells of the human placenta. To date there has been no systematic correlation of placental genotype and phenotype as a function of gestational age. Therefore, it is difficult to evaluate the impact on pregnancy outcome of aneuploidies observed in pre-implantation-stage human embryos. Additionally, the majority of genetic studies have focused on the placenta proper. As a result, little is known about the karyotype/genotype of the unusual subpopulation of fetal cytotrophoblasts that invade the uterine wall. Accordingly, the goals of the proposed research are to determine the frequency of specific chromosome aneuploidies in placental cells, including invasive cytotrophoblasts, from four weeks of gestation to term. The impact of alterations in the normal karyotype/genotype on cytotrophoblast apoptosis and differentiation, as well as immune interactions at the maternal-fetal interface, will also be examined. At the conclusion of the proposed training program, the candidate will be in an ideal position to establish a career as an independent investigator in placental cell biology with a focus on genetics. Future research directions include studies of whether particular genetic abnormalities are associated with specific pregnancy complications.